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ProtTrans: Toward Understanding the Language of Life Through Self-Supervised Learning
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Abstract
Computational biology and bioinformatics provide vast data gold-mines from protein sequences, ideal for Language Models (LMs) taken from Natural Language Processing (NLP). These LMs reach for new prediction frontiers at low inference costs. Here, we trained two auto-regressive models (Transformer-XL, XLNet) and four auto-encoder models (BERT, Albert, Electra, T5) on data from UniRef and BFD containing up to 393 billion amino acids. The protein LMs (pLMs) were trained on the Summit supercomputer using 5616 GPUs and TPU Pod up-to 1024 cores. Dimensionality reduction revealed that the raw pLM-embeddings from unlabeled data captured some biophysical features of protein sequences. We validated the advantage of using the embeddings as exclusive input for several subsequent tasks: (1) a per-residue (per-token) prediction of protein secondary structure (3-state accuracy Q3=81%-87%); (2) per-protein (pooling) predictions of protein sub-cellular location (ten-state accuracy: Q10=81%) and membrane versus water-soluble (2-state accuracy Q2=91%). For secondary structure, the most informative embeddings (ProtT5) for the first time outperformed the state-of-the-art without multiple sequence alignments (MSAs) or evolutionary information thereby bypassing expensive database searches. Taken together, the results implied that pLMs learned some of the grammar of the language of life. All our models are available through https://github.com/agemagician/ProtTrans.
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“Fine-tuning has not been extensively explored in previous work5, possibly due to its demanding computational requirements.”
From Nucleotide Transformer: building and evaluating robust foundation models for human genomics (2025) · cites this paper as [5]
In the citing paper
“We also noted that the highest model performance is never achieved by using embeddings from the final layer, as shown in earlier work5.”
From Nucleotide Transformer: building and evaluating robust foundation models for human genomics (2025) · cites this paper as [5]
In the citing paper
“Such models were then applied to protein sequence: the BERT architecture was directly trained on the Uniref100 and BFD-100 datasets to create the ProtBERT model [58] for protein sequence prediction.”
From Computational and artificial intelligence-based methods for antibody development (2023) · cites this paper as [58]
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“ProtTrans trained two autoregressive models (Transformer-X and XLNet) and four auto-encoder models (BERT, Albert, Electra, and T5) using more than two thousand million protein sequences, making it the state-of-the-art method to encode the protein sequence with the highest quality embeddings.”
BackgroundMethodInfluential
Metadata
- Authors
- Elnaggar, A., Heinzinger, M., Dallago, C., Rehawi, G., Wang, Y., Jones, L., Gibbs, T., Feher, T., Angerer, C., Steinegger, M., Bhowmik, D., & Rost, B.
- Affiliations
- Technical University of Munich (DE)
- Jiangnan University (CN)
- Google (United States) (US)
- Nvidia (United States) (US)
- NVIDIA, Santa Clara, CA, USA
- Seoul National University (KR)
- Oak Ridge National Laboratory (US)
- ORCID
- Venue
- IEEE Transactions on Pattern Analysis and Machine Intelligence
- Published
- 2022-10-01
- Volume
- 44
- Issue
- 10
- Pages
- 7112-7127
- ISSN
- 0162-8828 (ISSN-L)
- 2160-9292
- 1939-3539
- OpenAlex
- W3177500196
- Cited by
- 2,329
- References
- 101
- Citations by year
- 2026: 664 · 2025: 750 · 2024: 533 · 2023: 257 · 2022: 100
- FWCI
- 71.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- IEEE Transactions on Pattern Analysis and Machine Intelligence (publishedVersion, cc-by)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Research Foundation of Korea (2019R1A6A1A10073437, NRF-2020M3A9G7103933)
- New Faculty Startup Fund and the Creative-Pioneering Researchers Program
- Seoul National University
- Oak Ridge National Laboratory
- U.S. Department of Energy (DE-AC05-00OR22725)
- TensorFlow Research Cloud
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- protein language models, self-supervised learning, protein embeddings, secondary structure prediction, protein localization, ProtT5, Transformer-XL, XLNet, BERT, BFD, dimensionality reduction, protein sequence representation
- MeSH terms
- Supervised Machine Learning, Algorithms, Natural Language Processing, Proteins, Computational Biology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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